Department of Neuropsychiatry, Tokyo Medical and Dental University and
Department of Sleep Disorders Research, Tokyo Institute of Psychiatry,
Tokyo,
Japan.

Norepinephrine (NE) is considered to play a permissive role in the
occurrence
of rapid eye movement (REM) sleep. Clonidine is an NE alpha-2-receptor
agonist,
which has been considered to act mainly on the autoreceptors of
presynaptic
noradrenergic neurons to reduce their release of NE. However, previous
studies
of clonidine effects on REM sleep have produced controversial results
and the
effects of clonidine remain uncertain. To clarify the pharmacological
effects
of clonidine on human sleep, the sleep electroencephalograms (EEG)
recorded
from 15 young normal subjects after a single administration of either a
low (25
micro g) or medium (150 micro g) dose of clonidine were examined, and
fast
Fourier transformation (FFT) spectral analyses of the C3-A2 EEG were
performed.
Low-dose clonidine significantly increased the amount of REM sleep and
decreased the amount of non-REM (NREM) sleep during the second
one-third of the
drug nights compared to the corresponding hours of baseline night
recordings.
In contrast, medium-dose clonidine significantly decreased REM and
increased
NREM on drug nights compared to baseline nights in the entire night.
The
opposite actions of low and medium doses of clonidine on NREM-REM
proportion
may indicate that low-dose clonidine mainly affects the
alpha-2-receptors on
locus coeruleus-NE neurons presynaptically, reducing the release of NE,
whereas
medium-dose clonidine acts more post-synaptically.

PMID: 15009817 [PubMed - as supplied by publisher]

Analysis: This is an interesting study because it
shows how
important it is to avoid thinking in strict mechanistic terms when
prescribing
medication.All too often, we think of
the mechanism of action of a drug as something that is always the same.Experience shows that medications affect
different people differently.This
study shows that different doses of the same medication can affect the
same
person in different ways, depending on the dose.

Sometimes patients come back to their doctor after
having
gotten a prescription, and report an unexpected outcome.Sometimes the doctor says, “that can’t
happen.”This leads to all kinds of
misunderstanding and hard feelings.This
study shows one mechanism for possible unexpected results.

It is important for doctors and patients to
understand that, in the case of an unexpected outcome, you start out
the analysis by recognizing
what happened.After making the
pertinent observations, you draw a hypothesis, then test the hypothesis
if
clinically appropriate.To start out be
saying “that can’t happen” is an unproductive strategy: you don’t start
with a conclusion,
you start with observation.

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The Corpus Callosum is an occasional journal of armchair musings, by an Ann Arbor reality-based, slightly-left-of-center regular guy who reserves the right to be highly irregular at times.
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